title: Chemistry of ecteinascidins. Part 4: preparation of 2'-N-acyl ecteinascidin 770 derivatives with improved cytotoxicity profiles.
abstract: We report herein eleven 2'-N-acyl derivatives that were prepared from ecteinascidin 770 (Et 770: 1b) via 18,6'-O-bisallyl protected compound (4) in excellent yields. 2'-N-Acyl derivatives (6a-k) generally showed higher cytotoxicity than 1b. Among them, 3-quinolineacyl derivative (6g) and 4-fluorocinnamoyl derivative (6h) exhibited approximately 50- and 70-fold higher cytotoxicity to the HCT116 human colon carcinoma cell line, respectively, than 1b. Both compounds are potent inhibitors of the in vitro growth of several tumor cells and are therefore promising leads for further optimization. We also report the transformation of 1b into Et 788 (3), which is the first example of an ecteinascidin derivative having a primary amide at C-21 position.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Meiji Pharmaceutical University.
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Tsujimoto
authors.forename: Witaya
authors.initials: W
authors.lastname: Lowtangkitcharoen
authors.forename: Nanae
authors.initials: N
authors.lastname: Mori
authors.forename: Waree
authors.initials: W
authors.lastname: Pangkruang
authors.forename: Ploenthip
authors.initials: P
authors.lastname: Putongking
authors.forename: Khanit
authors.initials: K
authors.lastname: Suwanborirux
authors.forename: Naoki
authors.initials: N
authors.lastname: Saito
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D049109:Cell Proliferation / Q000187:drug effects; D045325:HCT116 Cells; D006576:Heterocyclic Compounds, 4 or More Rings / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D006801:Humans; D007546:Isoquinolines / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D009682:Magnetic Resonance Spectroscopy; D008968:Molecular Conformation; D013329:Structure-Activity Relationship; D014561:Urochordata / Q000737:chemistry / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D006576:Heterocyclic Compounds, 4 or More Rings; D007546:Isoquinolines; C464992:ecteinascidin 770